Stochastic sequence-level model of coupled transcription and translation in prokaryotes

BMC Bioinformatics

Research Article

Jarno Mäkelä¹  Andre S Ribeiro¹  Jason Lloyd-Price¹  Olli Yli-Harja² 

[1] Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, 33101, Tampere, FI, Finland;Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, 33101, Tampere, FI, Finland;Institute for Systems Biology, 1441N 34th St, 98103-8904, Seattle, WA, USA;

关键词: Translation Initiation;    Synonymous Codon;    Ribosome Binding Site;    Transcription Elongation;    Stochastic Simulation Algorithm;   

DOI  :  10.1186/1471-2105-12-121

 received in 2010-11-19, accepted in 2011-04-26,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundIn prokaryotes, transcription and translation are dynamically coupled, as the latter starts before the former is complete. Also, from one transcript, several translation events occur in parallel. To study how events in transcription elongation affect translation elongation and fluctuations in protein levels, we propose a delayed stochastic model of prokaryotic transcription and translation at the nucleotide and codon level that includes the promoter open complex formation and alternative pathways to elongation, namely pausing, arrests, editing, pyrophosphorolysis, RNA polymerase traffic, and premature termination. Stepwise translation can start after the ribosome binding site is formed and accounts for variable codon translation rates, ribosome traffic, back-translocation, drop-off, and trans-translation.ResultsFirst, we show that the model accurately matches measurements of sequence-dependent translation elongation dynamics. Next, we characterize the degree of coupling between fluctuations in RNA and protein levels, and its dependence on the rates of transcription and translation initiation. Finally, modeling sequence-specific transcriptional pauses, we find that these affect protein noise levels.ConclusionsFor parameter values within realistic intervals, transcription and translation are found to be tightly coupled in Escherichia coli, as the noise in protein levels is mostly determined by the underlying noise in RNA levels. Sequence-dependent events in transcription elongation, e.g. pauses, are found to cause tangible effects in the degree of fluctuations in protein levels.

【 授权许可】

Unknown   
© Mäkelä et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.